Lipid Bilayer Nanopore Control for Slower ssDNA Translocation
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Solution Overview
Problem
Existing nanopore membrane devices struggle to discriminate single base pairs in DNA sequencing due to rapid passage of ssDNA molecules under electrical potential, and existing tethering methods are cumbersome for small sample sizes.
Innovation Solution
Apply a sequence of electrical stimuli to manipulate and characterize molecules within a nanopore, including acquiring, holding, progression, and reverse progression stimuli, allowing for detailed characterization without extensive sample preparation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If an electrical potential is applied to attract ssDNA into the nanopore, then the ssDNA molecule is drawn into the nanopore for analysis, but the ssDNA molecule passes through the nanopore very quickly making analysis difficult
Solution Approach 1:
The patent applies periodic electrical stimuli including acquiring stimuli to capture ssDNA, holding stimuli to maintain the molecule in the nanopore, and progression stimuli to advance the molecule through the pore in a controlled, stepwise manner. This periodic application of different electrical conditions allows the ssDNA to be analyzed base-pair by base-pair with sufficient residence time for detection, rather than passing through too quickly in a single continuous motion.
2Measurement precision
If tethering methods are used to arrest ssDNA movement through the nanopore, then the ssDNA can be analyzed in detail, but extensive sample preparation is required which is not suitable for small sample sizes
Solution Approach 1:
The patent employs a feedback control system that automatically detects when ssDNA enters the nanopore through monitoring ionic current changes, and autonomously applies the appropriate sequence of electrical stimuli (acquiring, holding, and progression stimuli) without requiring manual intervention or complex sample preparation steps. The system self-regulates the analysis process, making it suitable for small sample sizes while maintaining high characterization accuracy.
3Productivity
If the electrical stimulus level is high to draw the molecule into the nanopore, then the molecule is captured efficiently, but the molecule progresses through the nanopore too quickly for detailed characterization
Solution Approach 1:
The patent dynamically adjusts the electrical stimulus level throughout the analysis process. It begins with high acquiring stimulus levels to efficiently capture and draw the molecule into the nanopore, then transitions to lower holding and progression stimulus levels that slow the molecule's movement through the pore. This dynamic adjustment of electrical conditions allows the system to achieve both high capture efficiency and detailed characterization accuracy at different stages of the analysis.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables high sensitivity and accuracy in DNA sequencing with improved signal-to-noise ratio and reduced sample requirements, suitable for applications like cancer biomarker screening and infectious disease detection.
Implementation Method 1
a small ion current due to conduction of ions across the nanopore can be observed
Implementation Method 2
the electrical potential needed to attract a ssDNA molecule in the nanopore
Implementation Method 3
it can partially or completely block the nanopore, causing a change in the magnitude of the current through the nanopore
Data Source
AI summary
Techniques for forming a nanopore in a lipid bilayer are described herein. In one example, an agitation stimulus level such as an electrical agitation stimulus is applied to a lipid bilayer wherein the agitation stimulus level tends to facilitate the formation of nanopores in the lipid bilayer. In some embodiments, a change in an electrical property of the lipid bilayer resulting from the formation of the nanopore in the lipid bilayer is detected, and a nanopore has formed in the lipid bilayer is determined based on the detected change in the lipid bilayer electrical property.